Protein Restriction for Diabetes

ABSTRACT

Treating a subject with at least one of diabetes, hyperinsulinemia, or glucose intolerance, can include: during a first low-protein time period of at least 4 consecutive days, administering nutrient material to the subject such that the subject has a bodily intake of protein of less than 20 grams per day and a bodily intake of carbohydrate of at least 40 percent of the subject&#39;s bodily intake of energy; and during a first normal-protein time period of at least 4 consecutive days that is after the low-protein period, administering to the subject a normal daily bodily intake of protein of at least 40 grams.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/295,704, filed Oct. 17, 2016, and entitled “Protein Restriction forCognitive Impairment,” which is a continuation of U.S. patentapplication Ser. No. 13/604,535, filed Sep. 5, 2012, now U.S. Pat. No.9,578,892, issued Feb. 28, 2017, which claims the priority benefit ofthe following four U.S. Provisional Applications 61/534,344, filed Sep.13, 2011; 61/621,959, filed Apr. 9, 2012; 61/671,591, filed Jul. 13,2012; and 61/679,782, filed Aug. 6, 2012; each of the last fiveforegoing applications entitled “Protein Restriction for DiseasePrevention and Treatment,” and the entirety of each of the foregoingapplications is incorporated herein by reference.

FIELD

The subject technology relates generally to human nutrition, health, anddisease prevention and treatment.

BACKGROUND

Macroautophagy (sometimes referred to herein as “autophagy”) is acellular “self-eating” process conserved among eukaryotic cells andinvolving digestion of cytoplasmic components via lysosomes. Duringstarvation, stimulation of autophagy can provide cells withmacronutrients to maintain metabolism and energy levels to survive.

SUMMARY

The subject technology is illustrated, for example, according to variousaspects described below. Various examples of aspects of the subjecttechnology are described as numbered clauses (1, 2, 3, etc.) forconvenience. These are provided as examples and do not limit the subjecttechnology. It is noted that any of the dependent clauses may becombined in any combination and placed into a respective independentclause or into other of the independent clauses. Other clauses can bepresented in a similar manner.

1. A method of preventing and/or treating disease, comprising:

-   -   (i) administering nutrients to a person such that the person's        dietary intake of protein is restricted to less than 40 grams        per day during a lower-protein period of at least two days;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's dietary intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

2. The method of clause 1, wherein the administering comprises providingto the person a plurality of meals.

3. The method of clause 1, wherein the administering comprises providingto the person a plurality of meals, at least two of which are configuredto be ingested by the person per day.

4. The method of clause 1, wherein the meals are substantially liquid.

5. The method of clause 1, wherein the meals comprise (a) lower-proteinmeals configured to be administered to the person during thelower-protein period and (b) higher-protein meals configured to beadministered to the person during the higher-protein period.

6. The method of clause 1, further comprising administering carbohydratein a sufficient amount to prevent a negative nitrogen balance exceeding5 grams of nitrogen per day.

7. The method of clause 1, further comprising administering carbohydratein a sufficient amount to prevent a negative nitrogen balance exceeding10 grams of nitrogen per day.

8. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 0.6 grams/kg body weight/day duringthe lower-protein period.

9. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 0.4 grams/kg body weight/day duringthe lower-protein period.

10. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 0.3 grams/kg body weight/day duringthe lower-protein period.

11. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 0.2 grams/kg body weight/day duringthe lower-protein period.

12. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 0.1 grams/kg body weight/day duringthe lower-protein period.

13. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 30 grams per day during thelower-protein period.

14. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 20 grams per day during thelower-protein period.

15. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 10 grams per day during thelower-protein period.

16. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to less than 5 grams per day during thelower-protein period.

17. The method of clause 1, wherein the person's dietary intake ofprotein is restricted to about zero grams per day during thelower-protein period.

18. The method of clause 1, wherein the lower-protein period is at least3 days.

19. The method of clause 1, wherein the lower-protein period is at least4 days.

20. The method of clause 1, wherein the lower-protein period is at least5 days.

21. The method of clause 1, wherein the lower-protein period is at least6 days.

22. The method of clause 1, wherein the lower-protein period is at least7 days.

23. The method of clause 1, wherein the lower-protein period is at least8 days.

24. The method of clause 1, wherein the lower-protein period is at least9 days.

25. The method of clause 1, wherein the lower-protein period is at least10 days.

26. The method of clause 1, wherein the lower-protein period is at least14 days.

27. The method of clause 1, wherein the lower-protein period is at least21 days.

28. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 0.8 grams/kg body weight/day during the higher-proteinperiod.

29. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 1.0 grams/kg body weight/day during the higher-proteinperiod.

30. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 1.2 grams/kg body weight/day during the higher-proteinperiod.

31. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 1.4 grams/kg body weight/day during the higher-proteinperiod.

32. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 1.6 grams/kg body weight/day during the higher-proteinperiod.

33. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 1.8 grams/kg body weight/day during the higher-proteinperiod.

34. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 2.0 grams/kg body weight/day during the higher-proteinperiod.

35. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 50 grams per day during the higher-protein period.

36. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 60 grams per day during the higher-protein period.

37. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 70 grams per day during the higher-protein period.

38. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 80 grams per day during the higher-protein period.

39. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 90 grams per day during the higher-protein period.

40. The method of clause 1, wherein the person's dietary intake ofprotein exceeds 100 grams per day during the higher-protein period.

41. The method of clause 1, wherein the higher-protein period is no morethan 14 days.

42. The method of clause 1, wherein the higher-protein period is no morethan 10 days.

43. The method of clause 1, wherein the higher-protein period is no morethan 7 days.

44. The method of clause 1, wherein the higher-protein period is no morethan 6 days.

45. The method of clause 1, wherein the higher-protein period is no morethan 5 days.

46. The method of clause 1, wherein the higher-protein period is no morethan 4 days.

47. The method of clause 1, wherein the higher-protein period is no morethan 3 days.

48. The method of clause 1, wherein the higher-protein period is no morethan 2 days.

49. The method of clause 1, wherein the higher-protein period is no morethan 1 day.

50. A system for preventing and/or treating disease, comprising:

-   -   food; and    -   instructions that a person eat the food according to the        following:        -   (i) during a lower-protein period of at least two days, the            person eats a lower-protein portion of the food, such that            the person's dietary intake of protein is restricted to less            than 40 grams per day; and        -   (ii) during a higher-protein period after the lower-protein            period, the person eats a higher-protein portion of the            food, such that the person's dietary intake of protein            exceeds 40 grams per day.

51. The system of clause 50, wherein the instructions further instructthat after the higher-protein period, the person repeat (i) and (ii).

52. The system of clause 50, wherein the food is substantially liquid.

53. The system of clause 50, wherein the food contains sufficientcarbohydrate to prevent a negative nitrogen balance exceeding 5 grams ofnitrogen per day in a person eating the food according to theinstructions.

54. The system of clause 50, wherein the food contains sufficientcarbohydrate to prevent a negative nitrogen balance exceeding 10 gramsof nitrogen per day in a person eating the food according to theinstructions.

55. The system of clause 50, wherein each of the lower-protein portionand the higher-protein portion comprise a plurality of meals configuredto be provided to the person.

56. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to be restricted to less than 0.6grams/kg body weight/day during the lower-protein period.

57. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to be restricted to less than 30grams per day during the lower-protein period.

58. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to be restricted to less than 20grams per day during the lower-protein period.

59. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to be restricted to less than 10grams per day during the lower-protein period.

60. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to be restricted to less than 5 gramsper day during the lower-protein period.

61. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to be restricted to about zero gramsper day during the lower-protein period.

62. The system of clause 50, wherein the lower-protein period is atleast 3 days.

63. The system of clause 50, wherein the lower-protein period is atleast 4 days.

64. The system of clause 50, wherein the lower-protein period is atleast 5 days.

65. The system of clause 50, wherein the lower-protein period is atleast 6 days.

66. The system of clause 50, wherein the lower-protein period is atleast 7 days.

67. The system of clause 50, wherein the lower-protein period is atleast 8 days.

68. The system of clause 50, wherein the lower-protein period is atleast 9 days.

69. The system of clause 50, wherein the lower-protein period is atleast 10 days.

70. The system of clause 50, wherein the lower-protein period is atleast 14 days.

71. The system of clause 50, wherein the lower-protein period is atleast 21 days.

72. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 0.8 grams/kg bodyweight/day during the higher-protein period.

73. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 1.0 grams/kg bodyweight/day during the higher-protein period.

74. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 1.2 grams/kg bodyweight/day during the higher-protein period.

75. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 1.4 grams/kg bodyweight/day during the higher-protein period.

76. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 1.6 grams/kg bodyweight/day during the higher-protein period.

77. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 50 grams per day during thehigher-protein period.

78. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 60 grams per day during thehigher-protein period.

79. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 70 grams per day during thehigher-protein period.

80. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 80 grams per day during thehigher-protein period.

81. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 90 grams per day during thehigher-protein period.

82. The system of clause 50, wherein the instructions provide for theperson's dietary intake of protein to exceed 100 grams per day duringthe higher-protein period.

83. The system of clause 50, wherein the higher-protein period is nomore than 14 days.

84. The system of clause 50, wherein the higher-protein period is nomore than 10 days.

85. The system of clause 50, wherein the higher-protein period is nomore than 7 days.

86. The system of clause 50, wherein the higher-protein period is nomore than 6 days.

87. The system of clause 50, wherein the higher-protein period is nomore than 5 days.

88. The system of clause 50, wherein the higher-protein period is nomore than 4 days.

89. The system of clause 50, wherein the higher-protein period is nomore than 3 days.

90. The system of clause 50, wherein the higher-protein period is nomore than 2 days.

91. The system of clause 50, wherein the higher-protein period is nomore than 1 day.

92. A system for preventing and/or treating disease, comprising:

-   -   food comprising higher-protein meals and lower-protein meals;        and    -   instructions that a person eat the food as follows:        -   (i) during a lower-protein period of at least two days, the            person eats the lower-protein meals such that the person's            dietary intake of protein is restricted to less than 30            grams per day; and        -   (ii) during a higher-protein period that follows the            lower-protein period and is no more than seven days, the            person eats the higher-protein meals such that the person's            dietary intake of protein exceeds 50 grams per day.

93. The system of clause 92, wherein the instructions further instructthat after the higher-protein period, the person repeat (i) and (ii).

94. The system of clause 92, wherein the lower-protein meals containsufficient carbohydrate to prevent a negative nitrogen balance exceeding10 grams of nitrogen per day in a person eating the food according tothe instructions.

95. The system of clause 92, wherein the lower-protein meals containsufficient carbohydrate to prevent a negative nitrogen balance exceeding5 grams of nitrogen per day in a person eating the food according to theinstructions.

96. The system of clause 92, wherein the lower-protein meals andhigher-protein meals are substantially liquid.

97. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having at least one of overweight,        obesity, hypertension, metabolic syndrome, type 2 diabetes,        hyperinsulinemia, or glucose intolerance, administering        nutrients to the person such that the person's bodily intake of        protein is restricted to less than 40 grams per day during a        lower-protein period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

98. The method of clause 97, wherein the lower-protein period is atleast two days.

99. The method of clause 97, wherein the diabetes comprises type 2diabetes.

100. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having at least one of Alzheimer's        disease, a genetic predisposition to a familial Alzheimer's        disease, or cognitive impairment, administering nutrients to the        person such that the person's bodily intake of protein is        restricted to less than 40 grams per day during a lower-protein        period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

101. The method of clause 100, wherein the lower-protein period is atleast two days.

102. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having at least one of a cancerous        or a precancerous neoplasia, administering nutrients to the        person such that the person's bodily intake of protein is        restricted to less than 40 grams per day during a lower-protein        period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

103. The method of clause 102, wherein the lower-protein period is atleast two days.

104. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having an infection by at least one        of a bacterium, a virus, a fungus, or a prion, administering        nutrients to the person such that the person's bodily intake of        protein is restricted to less than 40 grams per day during a        lower-protein period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

105. The method of clause 104, wherein the lower-protein period is atleast two days.

106. The method of clause 104, wherein the person is infected withMycobacterium tuberculosis.

107. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) selecting a person having an autoimmune disorder;    -   (ii) administering nutrients to the person such that the        person's bodily intake of protein is restricted to less than 40        grams per day during a lower-protein period of at least one day;    -   (iii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iv) after the higher-protein period, repeating (i) and (ii).

108. The method of clause 105, wherein the lower-protein period is atleast two days.

109. The method of clause 105, wherein the autoimmune disorder comprisesat least one of thyroiditis, hyperthyroidism, or hypothyroidism.

110. The method of clause 105, wherein the autoimmune disorder comprisesa Human Leukocyte Antigen (HLA) B27 associated disease.

111. The method of clause 105, wherein the autoimmune disorder comprisesmultiple sclerosis.

112. The method of clause 105, wherein the autoimmune disorder comprisesat least one of rheumatoid arthritis, ankylosing spondylitis, ananterior uveitis, or psoriatic arthritis.

113. The method of clause 105, wherein the autoimmune disorder comprisestype 1 diabetes.

114. The method of clause 105, wherein the autoimmune disorder comprisesCrohn's disease.

115. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) selecting a person having at least one of an inflammatory        bowel disease or an increased risk of an inflammatory bowel        disease;    -   (ii) administering nutrients to the person such that the        person's bodily intake of protein is restricted to less than 40        grams per day during a lower-protein period of at least one day;    -   (iii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iv) after the higher-protein period, repeating (i) and (ii).

116. The method of clause 115, wherein the lower-protein period is atleast two days.

117. The method of clause 115, wherein the inflammatory bowel diseasecomprises Crohn's disease.

118. The method of clause 115, wherein the inflammatory bowel diseasecomprises ulcerative colitis.

119. A method of slowing a rate of accumulation of mitochondrial damagein a mammal, comprising:

-   -   (i) administering nutrients to the mammal such that the mammal's        bodily intake of protein is restricted to less than 40 grams per        day during a lower-protein period of at least one day;    -   (iii) after the lower-protein period, administering nutrients to        the mammal such that the mammal's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iv) after the higher-protein period, repeating (i) and (ii).

120. The method of clause 119, wherein the lower-protein period is atleast two days.

121. The method of clause 119, wherein the damage comprises DNAoxidation.

122. The method of clause 119, wherein the damage comprises a DNAmutation.

123. The method of clause 119, wherein the damage comprises an RNAmutation.

124. A system for preventing and/or treating disease, comprising:

-   -   nutrient material administrable to at least one of a person's        gastrointestinal tract or intravascular space and comprising (a)        at least one of lipid or carbohydrate and (b) at least one        higher-protein portion and at least one lower-protein portion;    -   wherein the material is configured to be administered to the        person in the following sequence:        -   (i) during a lower-protein period of at least two days, the            person receives the at least one lower-protein portion such            that the person's bodily intake of protein is restricted to            less than 0.4 mg/kg of the person's bodyweight per day; and        -   (ii) during a higher-protein period that is after the            lower-protein period and is at least one day, the person            receives the at least one higher-protein portion such that            the person's bodily intake of protein exceeds 0.6 mg/kg of            the person's bodyweight per day.

125. The system of clause 124, further comprising instructions that thematerial be administered according to the sequence.

126. The system of clause 124, wherein the material is configured to beadministered to the person orally.

127. The system of clause 124, wherein the material is configured to beadministered to the person parenterally.

128. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) administering nutrients to a person such that the person's        bodily intake of protein is restricted to less than 40 grams per        day during a lower-protein period of at least two days;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

129. The method of clause 128, wherein the administering during at leastone of the lower-protein period or the higher-protein period isconfigured for oral ingestion of nutrients by the person.

130. The method of clause 128, wherein the administering during at leastone of the lower-protein period or the higher-protein period comprisesparenteral administration of nutrients to the person.

131. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) administering nutrients to a person such that the person's        bodily intake of protein is restricted to less than 0.4 mg/kg of        the person's bodyweight per day during a lower-protein period of        at least two days;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 0.6 mg/kg of the person's bodyweight per day during a        higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

132. The method of clause 131, wherein the administering during at leastone of the lower-protein period or the higher-protein period isconfigured for oral ingestion of nutrients by the person.

133. The method of clause 131, wherein the administering during at leastone of the lower-protein period or the higher-protein period comprisesparenteral administration of nutrients to the person.

134. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) administering nutrients to a person such that the person's        bodily intake of protein is restricted to less than the U.S.        recommended daily intake of protein during a lower-protein        period of at least two days;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein meets        or exceeds the U.S. recommended daily intake of protein during a        higher-protein period of at least two days; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

135. The method of clause 134, wherein the administering during at leastone of the lower-protein period or the higher-protein period isconfigured for oral ingestion of nutrients by the person.

136. The method of clause 134, wherein the administering during at leastone of the lower-protein period or the higher-protein period comprisesparenteral administration of nutrients to the person.

137. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having, or being at risk for,        age-related macular degeneration, administering nutrients to the        person such that the person's bodily intake of protein is        restricted to less than 40 grams per day during a lower-protein        period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

138. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having age-related macular        degeneration, administering nutrients to the person such that        the person's bodily intake of protein is restricted to less than        0.4 mg/kg of the person's bodyweight per day during a        lower-protein period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 0.6 mg/kg of the person's bodyweight per day during a        higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

139. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having had an ischemic impairment        of the person's neurologic function, administering nutrients to        the person such that the person's bodily intake of protein is        restricted to less than 0.4 mg/kg of the person's bodyweight per        day during a lower-protein period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 0.6 mg/kg of the person's bodyweight per day during a        higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

140. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having an atrial dysrhythmia,        administering nutrients to the person such that the person's        bodily intake of protein is restricted to less than 0.4 mg/kg of        the person's bodyweight per day during a lower-protein period of        at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 0.6 mg/kg of the person's bodyweight per day during a        higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

141. The method of clause 140, wherein the atrial dysrhythmia comprisesat least one of atrial fibrillation or atrial flutter.

142. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having a ventricular dysrhythmia,        administering nutrients to the person such that the person's        bodily intake of protein is restricted to less than 0.4 mg/kg of        the person's bodyweight per day during a lower-protein period of        at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 0.6 mg/kg of the person's bodyweight per day during a        higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

143. The method of clause 142, wherein the ventricular dysrhythmiacomprises at least one of ventricular fibrillation or ventriculartachycardia.

144. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having a ventricular dysrhythmia,        administering nutrients to the person such that the person's        bodily intake of protein is restricted to less than 0.4 mg/kg of        the person's bodyweight per day during a lower-protein period of        at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 0.6 mg/kg of the person's bodyweight per day during a        higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

145. The method of clause 142, wherein the ventricular dysrhythmiacomprises at least one of ventricular fibrillation or ventriculartachycardia.

146. A method for providing nutrients to a person to maintain or enhancehealth, comprising:

-   -   to a person selected for having, or being at risk for, male        pattern baldness, providing nutrient material administrable to        at least one of the person's gastrointestinal tract or        intravascular space and comprising at least one of lipid or        carbohydrate;    -   wherein all of any protein in the material constitutes less than        5 percent of a caloric content of the material;    -   instructing that the material be administered to the person such        that the person's bodily intake of all protein is restricted to        less than 30 grams per day during a lower-protein time period of        at least 48 hours.    -   instructing that carbohydrate be, or may be, administered to the        person such that the person's bodily intake of carbohydrate is        at least 40 grams per day during the lower-protein period; and    -   instructing that, during a higher-protein time period that is        after the lower-protein period and is at least 24 hours, the        person receives a higher bodily intake of protein than the        person received during the lower-protein period.

147. A method for providing nutrients to a person to maintain or enhancehealth, comprising:

-   -   providing nutrient material administrable to at least one of a        person's gastrointestinal tract or intravascular space and        comprising at least one of lipid or carbohydrate;    -   wherein all of any protein in the material constitutes less than        5 percent of a caloric content of the material;    -   instructing that the material be administered to the person such        that the person's bodily intake of all protein is restricted to        less than 30 grams per day during a lower-protein time period of        at least 48 hours.    -   instructing that carbohydrate be, or may be, administered to the        person such that the person's bodily intake of carbohydrate is        at least 40 grams per day during the lower-protein period; and    -   instructing that, during a higher-protein time period that is        after the lower-protein period and is at least 24 hours, the        person receives a higher bodily intake of protein than the        person received during the lower-protein period.

148. The method of clause 147, further comprising instructing that theperson receives an average daily bodily intake of all protein during thehigher-protein period that is at least 40 grams.

149. The method of clause 147, further comprising instructing that nosubstantial source of protein be administered to the person during thelower-protein period.

150. The method of clause 147, further comprising instructing that theperson's bodily intake of carbohydrate be restricted to less than 60grams per day during the higher-protein period.

151. The method of clause 147, further comprising instructing that theperson's bodily intake of carbohydrate be restricted to less than 50grams per day during the higher-protein period.

152. The method of clause 147, further comprising instructing that theperson's bodily intake of carbohydrate be restricted to less than 40grams per day during the higher-protein period.

153. The method of clause 147, further comprising instructing that theperson's bodily intake of carbohydrate be restricted to less than 30grams per day during the higher-protein period.

154. The method of clause 147, further comprising instructing that theperson's bodily intake of carbohydrate be restricted to less than 20grams per day during the higher-protein period.

155. The method of clause 147, further comprising instructing that theperson's bodily intake of carbohydrate be restricted to less than 10grams per day during the higher-protein period.

156. The method of clause 147, further comprising instructing that theperson's bodily intake of carbohydrate be restricted to substantiallyzero grams per day during the higher-protein period.

157. The method of clause 147, wherein the material comprises at leastsome of the carbohydrate administered to the person during thelower-protein period.

158a. The method of clause 147, wherein the providing the materialcomprises providing individually packaged servings of the material, andthe all of any protein in the material constitutes no more than 15 gramsper serving.

158b. The method of clause 147, wherein the providing the materialcomprises providing individually packaged servings of the material, andthe all of any protein in the material constitutes no more than 10 gramsper serving.

158c. The method of clause 147, wherein the providing the materialcomprises providing individually packaged servings of the material, andthe all of any protein in the material constitutes no more than 5 gramsper serving.

158d. The method of clause 147, wherein the providing the materialcomprises providing individually packaged servings of the material, andthe all of any protein in the material constitutes about zero grams perserving.

159. The method of clause 147, wherein the material is configured to beadministered to the person orally.

160. The method of clause 147, wherein the material is configured to beadministered to the person parenterally.

161. The method of clause 147, wherein material comprises carbohydrate,and the instructing that carbohydrate be, or may be, administered to theperson comprises instructing that the material be administered to theperson such that the person's bodily intake of carbohydrate in thematerial is at least 40 grams per day during the lower-protein period.

162. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 20 grams per day duringthe lower-protein period.

163. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 10 grams per day duringthe lower-protein period.

164. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to about zero grams per day duringthe lower-protein period.

165a. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 0.1 g per kilogram ofthe person's bodyweight per day during the lower-protein period.

165b. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 0.2 g per kilogram ofthe person's bodyweight per day during the lower-protein period.

165c. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 0.3 g per kilogram ofthe person's bodyweight per day during the lower-protein period.

165d. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 0.4 g per kilogram ofthe person's bodyweight per day during the lower-protein period.

165e. The method of clause 147, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 0.5 g per kilogram ofthe person's bodyweight per day during the lower-protein period.

166. The method of clause 147, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 50 grams.

167. The method of clause 147, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 60 grams.

168. The method of clause 147, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 70 grams.

169. The method of clause 147, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.5 g per kilogram of the person's body weight.

170. The method of clause 147, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.6 g per kilogram of the person's body weight.

171. The method of clause 147, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.7 g per kilogram of the person's body weight.

172. The method of clause 147, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.8 g per kilogram of the person's body weight.

173. The method of clause 147, wherein the lower-protein period is atleast 3 days.

174. The method of clause 147, wherein the lower-protein period is atleast 4 days.

175. The method of clause 147, wherein the lower-protein period is atleast 5 days.

176. The method of clause 147, wherein the lower-protein period is atleast 6 days.

177. The method of clause 147, wherein the lower-protein period is atleast 7 days.

178. The method of clause 147, wherein the higher-protein period is nomore than 14 days.

179. The method of clause 147, wherein the higher-protein period is nomore than 10 days.

180. The method of clause 147, wherein the higher-protein period is nomore than 7 days.

181. The method of clause 147, wherein the higher-protein period is nomore than 6 days.

182. The method of clause 147, wherein the higher-protein period is nomore than 5 days.

183. The method of clause 147, wherein the higher-protein period is nomore than 4 days.

184. The method of clause 147, wherein the higher-protein period is nomore than 3 days.

185. The method of clause 147, wherein the higher-protein period is nomore than 2 days.

186. A method for providing nutrients to a person to maintain or enhancehealth, comprising:

-   -   providing nutrient material administrable to at least one of a        person's gastrointestinal tract or intravascular space and        comprising at least one of lipid or carbohydrate;    -   wherein all of any protein in the material constitutes less than        5 percent of a caloric content of the material;    -   instructing that the material be administered to the person such        that the person's bodily intake of at least one of protein,        peptides, or amino acids is restricted to less than 30 grams per        day during a lower-protein time period of at least 48 hours;    -   instructing that carbohydrate be, or may be, administered to the        person such that the person's bodily intake of carbohydrate is        at least 40 grams per day during the lower-protein period; and    -   instructing that, during a higher-protein time period that is        after the lower-protein period and is at least 24 hours, the        person receives a higher bodily intake of protein than the        person received during the lower-protein period, such that the        average daily bodily intake of all protein during the        higher-protein period is at least 40 grams.

187. A method for providing nutrients to a person to maintain or enhancehealth, comprising:

-   -   providing nutrient material administrable to at least one of a        person's gastrointestinal tract or intravascular space and        comprising at least one of lipid or carbohydrate;    -   wherein all of any protein in the material constitutes less than        5 percent of a caloric content of the material;    -   instructing that the material be administered to the person such        that the person's bodily intake of all protein is restricted to        less than 30 grams per day during a lower-protein time period of        at least 48 hours;    -   instructing that carbohydrate be administered to the person such        that the person's bodily intake of carbohydrate is at least 40        grams per day, and is not limited to 150 grams per day, during        the lower-protein period; and    -   instructing that, during a higher-protein time period that is        after the lower-protein period and is at least 24 hours, the        person receives a higher bodily intake of protein than the        person received during the lower-protein period.

188. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 200 grams per day during thelower-protein period.

189. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 250 grams per day during thelower-protein period.

190. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 300 grams per day during thelower-protein period.

191. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 350 grams per day during thelower-protein period.

192. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 400 grams per day during thelower-protein period.

193. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 500 grams per day during thelower-protein period.

194. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 600 grams per day during thelower-protein period.

195. The method of clause 187, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is not limited to 700 grams per day during thelower-protein period.

196. A method for providing nutrients to a person to maintain or enhancehealth, comprising:

-   -   (a) providing nutrient material administrable to at least one of        a person's gastrointestinal tract or intravascular space and        comprising at least one of lipid or carbohydrate;    -   (b) wherein all of any protein in the material constitutes no        more than 10 percent of a caloric content of the material;    -   (c) instructing that the material be administered to the person        such that the person's bodily intake of all protein is        restricted to less than 30 grams per day during a lower-protein        time period of at least 48 hours;    -   (d) instructing that nutrition be administered to the person        such that the person's bodily intake of carbohydrate constitutes        at least 40% of the person's bodily intake of calories during        the lower-protein period; and    -   (e) instructing that, during a higher-protein time period that        is after the lower-protein period and is at least 24 hours, the        person receives a higher daily bodily intake of protein than the        person received during the lower-protein period.

196a. The method of clause 196, further comprising repeating steps (c)and (e).

196aa. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 5 percent of theperson's bodily intake of calories during the lower-protein.

196b. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 10 percent of theperson's bodily intake of calories during the lower-protein.

196c. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 15 percent of theperson's bodily intake of calories during the lower-protein.

196d. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 20 percent of theperson's bodily intake of calories during the lower-protein.

196e. The method of clause 196, wherein the all of any protein in thematerial constitutes no more than 8 percent of the caloric content ofthe material.

196f. The method of clause 196, wherein the all of any protein in thematerial constitutes no more than 5 percent of the caloric content ofthe material.

196g. The method of clause 196, wherein the all of any protein in thematerial constitutes no more than 3 percent of the caloric content ofthe material.

197. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate constitutes at least 50 percent of the person'sbodily intake of calories during the lower-protein period.

198. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate constitutes at least 60 percent of the person'sbodily intake of calories during the lower-protein period.

199. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate constitutes at least 70 percent of the person'sbodily intake of calories during the lower-protein period.

200. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate constitutes at least 80 percent of the person'sbodily intake of calories during the lower-protein period.

201. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate constitutes at least 90 percent of the person'sbodily intake of calories during the lower-protein period.

202. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 40 grams per day during thelower-protein period.

203. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 60 grams per day during thelower-protein period.

204. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 80 grams per day during thelower-protein period.

205. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 100 grams per day during thelower-protein period.

206. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 120 grams per day during thelower-protein period.

207. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 140 grams per day during thelower-protein period.

208. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 160 grams per day during thelower-protein period.

209. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 180 grams per day during thelower-protein period.

210. The method of clause 196, further comprising instructing thatcarbohydrate be administered to the person such that the person's bodilyintake of carbohydrate is at least 200 grams per day during thelower-protein period.

211. The method of clause 196, wherein carbohydrate in the materialconstitutes at least 50 percent of the caloric content of the material.

212. The method of clause 196, wherein carbohydrate in the materialconstitutes at least 60 percent of the caloric content of the material.

213. The method of clause 196, wherein carbohydrate in the materialconstitutes at least 70 percent of the caloric content of the material.

214. The method of clause 196, wherein carbohydrate in the materialconstitutes at least 80 percent of the caloric content of the material.

215. The method of clause 196, wherein carbohydrate in the materialconstitutes at least 90 percent of the caloric content of the material.

216. The method of clause 196, further comprising instructing that theperson receives an average daily bodily intake of all protein during thehigher-protein period that is at least 40 grams.

217. The method of clause 196, further comprising instructing that nosubstantial source of protein be administered to the person during thelower-protein period.

218. The method of clause 196, wherein the material comprises at leastsome of the carbohydrate administered to the person during thelower-protein period.

219. The method of clause 196, wherein the providing the materialcomprises providing individually packaged servings of the material, andthe all of any protein in the material constitutes no more than 15 gramsper serving.

220. The method of clause 196, wherein the material is configured to beadministered to the person orally.

221. The method of clause 196, wherein the material is configured to beadministered to the person parenterally.

222. The method of clause 196, wherein material comprises carbohydrate,and further comprising instructing that the material be administered tothe person such that the person's bodily intake of carbohydrate in thematerial is at least 40 grams per day during the lower-protein period.

223. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 20 grams per day duringthe lower-protein period.

224. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 10 grams per day duringthe lower-protein period.

225. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to about zero grams per day duringthe lower-protein period.

226. The method of clause 196, further comprising instructing that thematerial be administered to the person such that the person's bodilyintake of all protein is restricted to less than 0.3 g per kilogram ofthe person's bodyweight per day during the lower-protein period.

227. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 40 grams.

228. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 50 grams.

229. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 60 grams.

230. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 70 grams.

231. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.5 g per kilogram of the person's body weight.

232. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.6 g per kilogram of the person's body weight.

233. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.7 g per kilogram of the person's body weight.

234. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives a bodily intake ofall protein of at least 0.8 g per kilogram of the person's body weight.

235. The method of clause 196, wherein the lower-protein period is atleast 3 days.

236. The method of clause 196, wherein the lower-protein period is atleast 4 days.

237. The method of clause 196, wherein the lower-protein period is atleast 5 days.

238. The method of clause 196, wherein the lower-protein period is atleast 6 days.

239. The method of clause 196, wherein the lower-protein period is atleast 7 days.

240. The method of clause 196, wherein the higher-protein period is nomore than 14 days.

241. The method of clause 196, wherein the higher-protein period is nomore than 10 days.

242. The method of clause 196, wherein the higher-protein period is nomore than 7 days.

243. The method of clause 196, wherein the higher-protein period is nomore than 6 days.

244. The method of clause 196, wherein the higher-protein period is nomore than 5 days.

245. The method of clause 196, wherein the higher-protein period is nomore than 4 days.

246. The method of clause 196, wherein the higher-protein period is nomore than 3 days.

247. The method of clause 196, wherein the higher-protein period is nomore than 2 days.

248. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives, within a periodof 6 hours or less, at least 90 percent of a bodily intake of allprotein received in a day.

249. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives, within a periodof 5 hours or less, at least 90 percent of a bodily intake of allprotein received in a day.

250. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives, within a periodof 4 hours or less, at least 90 percent of a bodily intake of allprotein received in a day.

251. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives, within a periodof 3 hours or less, at least 90 percent of a bodily intake of allprotein received in a day.

252. The method of clause 196, further comprising instructing that,during the higher-protein period, the person receives, within a periodof 2 hours or less, at least 90 percent of a bodily intake of allprotein received in a day.

253. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having at least one of        osteoporosis, osteopenia, or a significant risk of osteoporosis,        administering nutrients to the person such that the person's        bodily intake of protein is restricted to less than 30 grams per        day during a lower-protein period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

254. A method of reducing at least one of a likelihood or a severity ofdisease, comprising:

-   -   (i) to a person selected for having chronic kidney disease,        administering nutrients to the person such that the person's        bodily intake of protein is restricted to less than 30 grams per        day during a lower-protein period of at least one day;    -   (ii) after the lower-protein period, administering nutrients to        the person such that the person's bodily intake of protein        exceeds 40 grams per day during a higher-protein period; and    -   (iii) after the higher-protein period, repeating (i) and (ii).

Additional features and advantages of the subject technology will be setforth in the description below, and in part will be apparent from thedescription, or may be learned by practice of the subject technology.The advantages of the subject technology will be realized and attainedby the structure particularly pointed out in the written description andclaims hereof as well as the appended drawings.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory and areintended to provide further explanation of the subject technology asclaimed.

DETAILED DESCRIPTION

In the following detailed description, numerous specific details are setforth to provide a full understanding of the subject technology. It willbe apparent, however, to one ordinarily skilled in the art that thesubject technology may be practiced without some of these specificdetails. In other instances, well-known structures and techniques havenot been shown in detail so as not to obscure the subject technology.

A phrase such as “an aspect” does not imply that such aspect isessential to the subject technology or that such aspect applies to allconfigurations of the subject technology. A disclosure relating to anaspect may apply to all configurations, or one or more configurations.An aspect may provide one or more examples of the disclosure. A phrasesuch as “an aspect” may refer to one or more aspects and vice versa. Aphrase such as “an embodiment” does not imply that such embodiment isessential to the subject technology or that such embodiment applies toall configurations of the subject technology. A disclosure relating toan embodiment may apply to all embodiments, or one or more embodiments.An embodiment may provide one or more examples of the disclosure. Aphrase such “an embodiment” may refer to one or more embodiments andvice versa. A phrase such as “a configuration” does not imply that suchconfiguration is essential to the subject technology or that suchconfiguration applies to all configurations of the subject technology. Adisclosure relating to a configuration may apply to all configurations,or one or more configurations. A configuration may provide one or moreexamples of the disclosure. A phrase such as “a configuration” may referto one or more configurations and vice versa. To the extent permitted bylaw, the contents of this disclosure, including any figures and text,are protected under U.S. copyright law, copyright 2011, 2012.

Autophagy is a homeostatic “self-eating” process that has been conservedamong eukaryotic cells and which involves the digestion of cytoplasmiccomponents via the lysosomal pathway. Under normal conditions, it allowscells to break down long-lived proteins, thus complementing the actionof the proteasome, which deals chiefly with short-lived proteins. Duringperiods of starvation, stimulation of autophagy is important to providecells exposed to nutrient deprivation with amino acids, glucose, andfatty acids to maintain metabolism and ATP levels compatible with cellsurvival.

Stimulation of autophagy plays a critical role in counteracting nutrientdeprivation following birth in newborn mice. Under basal conditions,autophagy helps the cell to get rid of damaged organelles, such asmitochondria and toxic aggregation-prone proteins. The functions ofautophagy are not limited to these aspects, but extend beyond, as shownby the discovery of its role in the innate and adaptive immuneresponses. Autophagy malfunction contributes to the pathogenesis of avariety of diseases, including cancer, neurodegenerative andcardiovascular disorders, and infectious diseases. Another importantaspect of autophagy in mammalian cells that remains to be unraveled isthe role of autophagy in cell death, which has been the topic of severalrecent reviews.

During autophagy, part of the cytoplasm containing long-lived proteinsor organelles is surrounded by a cisternal membrane, designated thephagophore by Seglen. The term “isolation membrane” is also used as asynonym of phagophore. The phagophore then closes to form adouble-membraned vacuole, known as the autophagosome. Autophagosomes usedynein motors to move along microtubules towards the microtubuleorganizing center, where they fuse with lysosomes to form autolysosomes.However, most of the autophagosomes receive input from the endocyticcompartments before they fuse with lysosomes.

Many AuTophaGy-related (ATG) genes identified in yeast by geneticscreens have mammalian counterparts, and 18 different Atg proteins areknown to be recruited to the isolation membrane, where they are involvedin autophagosome formation. The origin of the membranes involved inautophagosome formation is unknown, but findings suggest the endoplasmicreticulum (ER) may be the source of lipids in the autophagosomalmembranes. Ktistakis and colleagues propose that autophagosomes areformed in a high-phosphatidylinositol 3-phosphate (PtdIns 3P),cup-shaped compartment known as the “omegasome” (from its omega-likeshape), which is dynamically connected to the ER. Electron tomographyanalyses demonstrate a direct connection between the ER and thephagophore.

Evidence supports the idea that autophagy can be regulated at severaldifferent physiologic levels: (1) signaling pathways acting upstream ofthe autophagy machinery; (2) formation of autophagosomes; and (3)maturation of autophagosomes and their fusion with lysosomes.

The existence of these different levels of autophagy regulation meansthat there are many different ways in which autophagy can be modulatedby compounds relevant to clinical interventions. Moreover, thestructural biology of Atg proteins is an expanding area of research thatshould not only reveal the mechanism of action of these proteins, butalso guide the design of drugs intended to modulate their activity.

Autophagy refers to the process by which lysosomes degrade intracellularconstituents, including both organelles and soluble proteins. Thisprocess is traditionally regarded as a cellular response to stresstypically related to nutrient deprivation, toxin exposure, infection, oroxidative stress.

In contrast to the ubiquitin-proteasome pathway which degrades mostlyshort-lived proteins, autophagy is mainly involved in breaking downproteins with long-half lives and damaged organelles. Some basic form ofthis machinery is highly conserved from yeast to mammals. Depending onhow lysosomes receive the cargo, autophagy can be further classifiedinto three types, namely macroautophagy, microautophagy, andchaperone-mediated autophagy (CMA).

Macroautophagy involves multiple steps beginning with induction andending with the release of the degraded products to the cytosol. It ischaracterized by the sequestration of cytosolic components in anautophagic vacuole or autophagosome, which fuses with lysosomal membraneto deliver its contents for degradation.

This double-membrane vacuole is the morphological hallmark of autophagy.The process is highly inducible in response to stress signals andregulated at various junctures by a large number of autophagy-related(ATG) genes, which involves controlling the activity of mTOR (mammaliantarget of rapamycin), a suppressor of macroautophagy. Microautophagy isless well studied than macroautophagy. Unlike macroautophagy,microautophagy does not involve the formation of double-membranevacuoles.

Rather, the defining feature of microautophagy is the invagination orexvagination of lysosomal membrane to sequester cytosolic components.Mitophagy is a term describing the selective sequestration and removalof mitochondria by either macro- or microautophagy.

Unlike macro- and microautophagy, CMA does not involve membranevacuoles. Rather, it is regulated by direct protein interaction. Two keyregulators, chaperone protein heat-shock cognate 70 (Hsc70) andlysosomal membrane receptor Lamp2A, control the CMA process.

Hsc70, in a complex with other co-chaperone proteins, binds to cytosolicproteins containing a pentapeptide targeting motif KFERQ and deliverssubstrate proteins to the surface of lysosomes. Binding of thischaperone-substrate complex to Lamp2A leads to the translocation ofsubstrates cross the lysosomal membrane. Both the level and availabilityof Lamp2A are regulated by stress signals, making Lamp2A one of themajor modes by which CMA activity is controlled.

Protein restriction, with or without caloric restriction, can affectdisease states and the rate of aging in an organism, such as a human, ina variety of ways including, but not limited to, (a) reducing the rateof production of free radicals (as reactive oxygen species) inmitochondria, leading to reduced oxidation and mutation rates inmitochondrial DNA and RNA; (b) decreasing the degree of membrane fattyacid unsaturation in cells, including in the mitochondrial innermembrane, lowering the susceptibility of membranes to oxidative damage;and (c) increasing autophagy, to repair or replace cellular structures,such as damaged organelles and proteins.

According to aspects of the subject technology, a physician, otherhealth care professional, or subject person can adjust the amount andduration of restriction and/or nonrestriction of protein administered tothe person. By following principles of the subject technology asdescribed herein, those of skill in the art can, without difficulty orundue experimentation, to adjust or titrate nutritional parameters, suchas daily protein intake and the number of days of protein restriction,to optimize the attainment in the person of such endpoints as diseaseprevention or amelioration. This is accomplished by, for example,observing the effect of any significant change in a pattern of theperson's protein intake over weeks to months. If signs of proteindeficiency appear in the person, such as cold intolerance,hypoalbuminemia, or particular changes in skin, hair, and/or nails, anamount of protein administered to the person can easily be increased.

According the subject technology, the degree of consumption orrestriction of a person's protein (or other macronutrient) intake may bespecified either in absolute or relative terms, such as by, e.g., dailyor weekly total intake, or in mass or weight of protein per mass orweight of a person or her fat mass or her lean mass (e.g., mg of protein(or other macronutrient) per kg of the person's bodyweight). All claimedmethods, compositions, and systems are intended to encompass any suchtype of specification. Thus, all methods and systems disclosed as one ofthe following two options (relative or absolute macronutrient intake)also includes the other:

First exemplary option: (i) during a lower-protein period, the personreceives a lower-protein portion such that the person's bodily intake ofprotein is restricted to less than 0.4 mg/kg of the person's bodyweightper day; and (ii) during a higher-protein period that is after thelower-protein period, the person receives a higher-protein portion suchthat the person's bodily intake of protein exceeds 0.6 mg/kg of theperson's bodyweight per day.

Second exemplary option: (i) administering nutrients to the person suchthat the person's bodily intake of protein is restricted to less than 40grams per day during a lower-protein period of at least one day; and(ii) after the lower-protein period, administering nutrients to theperson such that the person's bodily intake of protein exceeds 40 gramsper day during a higher-protein period.

Some aspects of the subject technology include a method for providingnutrients to a person to maintain or enhance health, comprising:providing nutrient material administrable to at least one of a person'sgastrointestinal tract or intravascular space and comprising at leastone of lipid or carbohydrate; wherein all of any protein in the materialconstitutes less than 5 percent of a caloric content of the material;instructing that the material be administered to the person such thatthe person's bodily intake of at least one of protein, peptides, oramino acids is restricted to less than 30 grams per day during alower-protein time period of at least 48 hours; instructing thatcarbohydrate be, or may be, administered to the person such that theperson's bodily intake of carbohydrate is at least 40 grams per dayduring the lower-protein period; and instructing that, during ahigher-protein time period that is after the lower-protein period and isat least 24 hours, the person receives a higher bodily intake of proteinthan the person received during the lower-protein period, such that theaverage daily bodily intake of all protein during the higher-proteinperiod is at least 40 grams.

In some embodiments, the lower-protein period can be at least 24 hours,at least 36 hours, at least 72 hours, at least 96 hours, at least 120hours, or similar minimum duration.

The inventor has found that autophagy in at least hepatocytes andneurons is unexpectedly stimulated to a beneficial degree during periodsof dietary protein restriction despite a concomitant dietarycarbohydrate intake of, e.g., at least 40 grams per day or at least 60percent of total caloric intake, and despite its attendant elevation ofinsulin. Elevated insulin has been previously thought to prevent,generally uniformly, autophagy or to prevent substantial increases inautophagy.

In some embodiments, the lower-protein time period is at least 36 hours.

Autophagy and Parkinson's Disease

Emerging evidence supports the view that dysregulation of autophagy maycontribute to the pathogenic process in Parkinson's disease (PD).Several genetic risk factors associated with PD have been connected todifferent forms of autophagy. This includes evidence demonstrating thatboth macroautophagy and CMA regulate a-synuclein. Furthermore, the CMAprocess can be disrupted by the a-synuclein A53T mutant. Similarly, ithas been shown that the ubiquitin C-terminal hydrolase L1 (UCH-L1)mutant I94M interrupts the CMA process by binding to Lamp2A withabnormally high affinity. Parkin has been shown to be re-localized tomitochondria following mitochondrial damage, which promotes mitophagy.

LRRK2 mutants have been recently found to induce the increase oraccumulation of autophagic vacuoles. Loss of PINK1 function has beenproposed to affect autophagy.

Strong experimental and epidemiological data exist to support anetiological role for neurotoxins in PD. There are hints that many ofthese toxins may also alter the process of autophagy. For example,mitochondrial complex I inhibitor rotenone can inhibit capacity ofautophagy. 6-OHDA up-regulates LC3 in nigral DA neurons. Paraquatinduces the accumulation of autophagic vacuoles.

These toxins may affect CMA. Some studies show that limited exposure to6-OHDA activates CMA by increasing the levels of Lamp2A.

Intracellular protein misfolding and aggregation are features of manylate-onset neurodegenerative diseases called proteinopathies. Theseinclude Alzheimer's disease, Parkinson's disease, tauopathies, andpolyglutamine expansion diseases [e.g., Huntington's disease and variousspinocerebellar ataxias (SCAs), like SCA3]. There are no effectivestrategies to slow or prevent the neurodegeneration resulting from thesediseases in humans. The mutations causing many proteinopathies (e.g.,polyglutamine diseases and tauopathies) confer novel toxic functions onthe specific protein, and disease severity frequently correlates withthe expression levels of the protein. Thus, the factors regulating thesynthesis and clearance of these aggregate-prone proteins are putativetherapeutic targets. The proteasome and autophagy-lysosomal pathways arethe major routes for mutant huntingtin fragment clearance. While thenarrow proteasome barrel precludes entry of oligomers and aggregates ofmutant huntingtin (or other aggregate-prone intracellular proteins),such substrates can be degraded by macroautophagy.

Rapamycin reduces levels of soluble and aggregated huntingtin andattenuates its toxicity in cells and in transgenic Drosophila and mousemodels.

The range of intracellular proteinopathy substrates that are cleared byautophagy includes other targets, including proteins mutated in certainSCAs, forms of synuclein mutated in familial forms of Parkinson'sdisease, and tau mutants that cause frontotemporal dementia/tauopathy.In this chapter, we consider the therapeutic potential of autophagyupregulation for various proteinopathies, and describe how this strategymay act both by removing the primary toxin (themisfolded/aggregate-prone protein) and by reducing susceptibility toapoptotic insults.

Proteinopathies

Intracellular protein misfolding and aggregation are features of manylate-onset neurodegenerative diseases called proteinopathies. Theseinclude Alzheimer's disease, Parkinson's disease, tauopathies, andvarious diseases caused by abnormally expanded tracts of the amino acidglutamine, like Huntington's disease (HD). HD is an autosomal-dominantneurodegenerative disorder caused by a CAG trinucleotide repeatexpansion, which results in an abnormally long polyglutamine (polyQ)tract in the N-terminus of huntingtin. Asymptomatic individuals have 35or fewer CAG repeats, while HD is caused by expansions of 36 or morerepeats.

HD belongs to a group of human neurodegenerative disorders caused by CAGrepeat/polyQ expansions, which includes spinocerebellar ataxias (SCAs)type 1, 2, 3, 6, 7, and 17, spinobulbar muscular dystrophy (SBMA), anddentatorubral pallidoluysian atrophy (DRPLA).

Autophagy is a bulk degradation process that involves the sequestrationof portions of cytoplasm by a double-membrane autophagosome, followed bydigestion of the sequestered material when the autophagosome fuses witha lysosome full of hydrolytic enzymes.

Researchers have found that loss of autophagy causes neurodegenerationeven in the absence of any disease-associated mutant proteins, whichsuggests that the continuous clearance of cellular proteins throughbasal autophagy prevents their accumulation, and in turn preventsneurodegeneration. Experiments in fly and mouse models have providedproof of principle that stimulation of autophagy can prevent and evenreverse neurodegenerative disease.

The compound that has been used for such studies, the immunosuppressantrapamycin, stimulates autophagy and aggregate digestion by inhibitingthe evolutionarily conserved protein kinase TOR (target of rapamycin).TOR acts as a brake on autophagy; thus, when it is inhibited withrapamycin, autophagy is turned on.

TOR does not control autophagy alone—it is also an activator of ribosomebiogenesis and other pathways involved in cell growth. This causesundesired side effects, such as immunosuppression, during long-termadministration of rapamycin, and therefore alternative inducers ofautophagy are desired.

Dietary restriction of total calories without malnutrition has beenshown to prolong life in rats, mice, dogs, fish, spiders, fleas, flies,worms, yeasts, and monkeys.

Dietary protein restriction can achieve many of the same effects ascalorie restriction, though protein restriction is generally bettertolerated by humans than severe calorie restriction.

One approach to treating and/or preventing any disease according to thesubject technology is to restrict protein markedly for a first period,then to resume normal protein feeding during a second period. Thisaccomplishes two goals: (1) stimulating autophagy during the firstperiod, thereby helping clear cells of debris; and (2) preventingprotein malnutrition during the second period.

In some embodiments, protein intake may be restricted for up to one day,followed by a period of differing protein intake. The subjecttechnology, however, also includes restricting protein for longerperiods, for at least two days, for example, followed by a period ofnormal to high protein intake. This produces the unexpected result ofachieving a more profound degree of autophagy in a subject withoutproducing protein deficiency, protein malnutrition, or protein-caloriemalnutrition. This longer duration of autophagy better assists inclearing cells of abnormal proteins (e.g., oxidized, glycated, andfructated proteins) and abnormal organelles, such as mitochondria andlysosomes. This can assist in preventing and treating diseases caused orexacerbated by an accumulation of cellular debris, such as in the heart,pancreas, liver, brain, and skeletal muscles, leading to organdysfunction.

Protein Restriction and Cancer

Protein restriction can be used according to the subject technology toenhance autophagy and, in some cases, induce cell death, throughapoptosis or otherwise, in patients with neoplasms that either benign(e.g., meningioma) or malignant (e.g., astrocytoma). In glioma cells,the drug minocycline induces nonapoptotic cell death, which isassociated with the presence of autophagic vacuoles in the cytoplasm.Minocycline induces autophagy, as confirmed by acridine orange,monodansylcadaverine (MDC) stainings of vesicle formation, and theconversion of microtubule-associated proteins light chain 3 (LC3-I) toLC3-II. Pretreatment with autophagy inhibitor 3-methyladenine (3-MA)suppresses induction of acidic vesicular organelles and the accumulationof LC3-II to the autophagosome membrane in glioma cells treated withminocycline. Despite the pretreatment of 3-MA, minocycline induces celldeath via apparent activation of caspase-3. Minocycline effectivelyinhibits tumor growth and induces autophagy in the xenograft tumor modelof C6 glioma cells. Thus, minocycline appears to kill glioma cells byinducing autophagic cell death. As a result, stimulation of autophagy byrestriction of protein intake according to principles of the subjecttechnology is a promising therapeutic intervention for malignant gliomasand other cancers.

Protein Restriction in Autoimmune Disorders

As used herein, an “autoimmune disorder” is any disorder known orsuspected by medical researchers to be related to self-targeting of amammalian (e.g., human) immune system, such that inflammation results.Each of the following disorders is known or suspected to be autoimmunein nature and can, in certain cases, be treated, prevented, and/or haveits severity or progression lessened in a person by restriction of theperson's bodily intake of protein according to methods and systems ofthe subject technology.

Accepted/ Suspected as Name of Disorder Autoimmune Acute disseminatedencephalomyelitis(ADEM) Accepted Addison's Disease AgammaglobulinemiaAlopecia areata Accepted Amyotrophic Lateral Sclerosis AnkylosingSpondylitis Accepted Antiphospholipid syndrome Accepted Antisynthetasesyndrome Atopic allergy Atopic dermatitis Autoimmune aplastic anemiaAutoimmune cardiomyopathy Accepted Autoimmune enteropathy Autoimmunehemolytic anemia Accepted Autoimmune hepatitis Accepted Autoimmune innerear disease Accepted Autoimmune lymphoproliferative syndrome AcceptedAutoimmune peripheral neuropathy Accepted Autoimmune pancreatitisAccepted Autoimmune polyendocrine syndrome Accepted Autoimmuneprogesterone dermatitis Accepted Autoimmune thrombocytopenic purpuraAccepted Autoimmune urticaria Accepted Autoimmune uveitis Accepted Balodisease/Balo concentric sclerosis Behçet's disease Berger's diseaseBickerstaff's encephalitis Blau syndrome Bullous pemphigoid CancerCastleman's disease Celiac disease Accepted Chagas disease SuspectedChronic inflammatory demyelinating polyneuropathy Chronic recurrentmultifocal osteomyelitis Chronic obstructive pulmonary disease SuspectedChurg-Strauss syndrome Cicatricial pemphigoid Cogan syndrome Coldaggiutinin disease Accepted Complement component 2 deficiency Contactdermatitis Cranial arteritis CREST syndrome Crohns Disease (one of twotypes of idiopathic Accepted inflammatory bowel disease “IBD”) Cushing'sSyndrome Cutaneous leukocytocstic angiitis Dego's disease Dercum'sdisease Suspected Dermatitis herpetiformis Dermatomyositis AcceptedDiabetes mellitus type 1 Accepted Diffuse cutaneous systemic sclerosisDressler's syndrome Drug-induced lupus Discoid lupus erythematosusEczema Endometriosis Suspected Enthesitis-related arthritis Eosinophilicfasciitis Accepted Eosinophilic gastroenteritis Epidermolysis bullosaacquisita Erythema nodosum Erthroblastosis fetalis Essential mixedcryoglobulinemia Evan's syndrome Fibrodysplasia ossificans progressivaFibrosing aveolitis akaIdiopathic_pulmonary_fibrosis GastritisGastrointestinal pemphigoid Accepted Giant cell arteritisGlomerulonephritis Sometimes Goodpasture's syndrome Accepted Grave'sdisease Accepted Guillain-Barré syndrome (GBS) Accepted Hashimoto'sencephalopathy Accepted Hashimoto's thyroiditis AcceptedHenoch-Schonlein purpura Herpes gestationis aka Gestational PemphigoidHidradenitis suppurativa Suspected Hypogammaglobulinemia IdiopathicInflammatory Demyelinating Diseases Idiopathic pulmonary fibrosisIdiopathic thrombocytopenic purpura (SeeAutoimmune Acceptedthrombocytopenic purpura) IgA nephropathy Inclusion body myositisChronic inflammatory demyelinating polyneuropathy Interstitial cystitisSuspected Juvenile idiopathic arthritis aka Juvenile rheumatoidarthritis Kawasaki's Disease Suspected Lambert-Eaton myasthenic syndromeLeukocytoclastic vasculitis Lichen planus Lichen sclerosus Linear IgAdisease (LAD) Lou Gehrig's disease (Also Amyotrophic lateral sclerosis)Lupoid hepatitis aka Autoimmune_hepatitis Lupus erythematosus AcceptedMajeed syndrome Ménière's disease Microscopic polyangiitis Miller-Fishersyndrome see Guillain-Barre_Syndrome Accepted Mixed Connective TissueDisease Accepted Morphea Suspected Mucha-Habermann disease akaPityriasis lichenoides et varioliformis acuta Multiple sclerosisSuspected Myasthenia gravis Accepted Myositis Narcolepsy SuspectedNeuromyelins optica (Also Devic's Disease) Neuromyotonia SuspectedOccular cicatricial pemphigoid Opsoclonus myoclonus syndrome SuspectedOrd's thyroiditis Palindromic rheumatism PANDAS (pediatric autoimmuneneuropsychiatric Suspected disorders associated with streptococcus)Paraneoplastic cerebellar degeneration Paroxysmal nocturnalhemoglobinuria (PNH) Sometimes Parry Romberg syndrome Parsonnage-Turnersyndrome Pars planitis Pemphigus vulgaris Accepted Pernicious anaemiaAccepted Perivenous encephalomyelitis POEMS syndrome Polyarteritisnodosa Polymyalgia rheumatica Polymyositis Accepted Primary biliarycirrhosis Accepted Primary sclerosing cholangitis Progressiveinflammatory neuropathy Suspected Psoriasis Accepted Psoriatic arthritisAccepted Pyoderma gangrenosum Pure red cell aplasia Rasmussen'sencephalitis Raynaud phenomenon Suspected Relapsing polychondritisAccepted Reiter's syndrome Restless leg syndrome SuspectedRetroperitoneal fibrosis Rheumatoid arthritis Accepted Rheumatic_feverSarcoidosis Suspected Schizophrenia Suspected Schmidt syndrome anotherform of APS Schnitzler syndrome Scleritis Scleroderma Suspected SerumSickness Sjögren's syndrome Accepted Spondyloarthropathy Still's diseasesee Juvenile Rheumatoid Arthritis Stiff person syndrome SuspectedSubacute bacterial endocarditis (SBE) Susac's syndrome Sweet's syndromeSydenham chorea (see PANDAS) Sympathetic ophthalmia Systemic lupuserythematosis see Lupus erythematosis Takayasu's arteritis Temporalarteritis (also known as “giant cell arteritis”) AcceptedThrombocytopenia Tolosa-Hunt syndrome Transverse myelitis AcceptedUlcerative colitis (one of two types of idiopathic Accepted inflammatorybowel disease “IBD”) Undifferentiated connective tissue diseasedifferentfrom Accepted Mixed connective tissue disease Undifferentiatedspondyloarthropathy Urticarial vasculitis Vasculitis Accepted VitiligoSuspected Wegener's granulomatosis Accepted

According to embodiments of the subject technology, by restrictingprotein intake in persons who have or are at risk for autoimmunedisorders, one can decrease cellular damage, decrease the susceptibilityof cells to damage, and, at least by increasing autophagy, increasecleanup of the damage in some cases.

Protein Restriction in Sequelae of Obesity, Hypertension, InsulinResistance, and Metabolic Syndrome

In both genetic and dietary models of obesity, one can observe a markeddownregulation of autophagy, particularly in Atg7 expression levels inliver. Suppression of Atg7 both in vitro and in vivo results indefective insulin signaling and elevated endoplasmic reticulum (ER)stress. In contrast, restoration of Atg7 expression in liver results indampened ER stress, enhanced hepatic insulin action, and systemicglucose tolerance in obese mice. Beneficial Atg7 restoration in obesemice can be prevented by blocking a downstream autophagy mediator, Atg5,supporting the concept of Atg7's dependence on autophagy for regulatinginsulin action. Thus, autophagy is an important regulator of organellefunction and insulin signaling, and loss of autophagy contributesstrongly to the defective insulin action of obesity, which in turn leadsto many known sequelae and is associated with, for example,hypertension, hyperlipidemia, hypercholesterolemia,hypertriglyceridemia, certain cancers, cholelithiasis, depression,coronary artery disease, peripheral vascular disease, type 2 diabetes,Alzheimer's disease, and other dementia syndromes.

Protein Restriction in Diabetes Mellitus

Type 2 diabetes mellitus is characterized by insulin resistance andfailure of pancreatic beta cells producing insulin. Mitochondrialdysfunction plays a role in both processes of diabetes. Autophagy, whichcan be upregulated by restriction of dietary energy and/or protein,maintains cellular homeostasis through degradation and recycling oforganelles such as mitochondria. As dysfunctional mitochondria are themain organelles removed by autophagy, one can observe the role ofautophagy in diabetes using mice with beta cell-specific deletion of,for example, the Atg7 gene. Atg7-mutant mice show reduction in beta cellmass and pancreatic insulin content. Electron microscopy shows swollenmitochondria and other ultrastructural changes in autophagy-deficientbeta cells. Insulin secretory function ex vivo is also impaired. As aresult, Atg7-mutant mice show hypoinsulinemia and hyperglycemia.Autophagy appears necessary to maintain structure, mass, and function ofbeta cells. Besides its effect on beta cells, autophagy affects insulinsensitivity because mitochondrial dysfunction is implicated in insulinresistance and autophagy is involved in the maintenance of organelles,including mitochondria. Furthermore, since aging is associated withimpaired glucose tolerance, decline of autophagic activity appears to beinvolved in age-associated reduction of glucose tolerance.

Protein Restriction in Infection

Autophagy acts an immune mechanism. One of the model systems showing howautophagy and more traditional immunity systems cooperate in defenseagainst intracellular pathogens is macrophage infection withMycobacterium tuberculosis. M. tuberculosis is a significant humanpathogen that latently infects billions of people and causes activedisease in millions of patients worldwide. The ability of the tuberclebacillus to persist in human populations rests upon its macrophageparasitism. Autophagy can act as a cell-autonomous innate immunitymechanism capable of eliminating intracellular bacteria, e.g., M.tuberculosis. Embodiments of the subject technology recognize that: (1)autophagy functions as an innate defense mechanism against intracellularmicrobes; (2) autophagy is under the control of pattern recognitionreceptors (PRR) such as Toll-like receptors (TLR), and it acts as animmunological output effector of PRR and TLR signaling; (3) autophagy isone of the effector functions associated with the immunity-regulatedGTPases, which are molecules involved in cell-autonomous defense; (4)autophagy is an immune effector of Th1/Th2 T cell responsepolarization—autophagy is activated by Th1 cytokines (acting in defenseagainst intracellular pathogens) and is inhibited by Th2 cytokines(making cells accessible to intracellular pathogens). As an ancientinnate immunity defense, autophagy became integrated over the course ofevolution with other immune mechanisms of increasing complexity.

Protein Restriction and Macular Degeneration

Age-related macular degeneration (AMD) is the major cause of blindnessin the elderly, over 1.75 million people having reduced vision due toAMD in the United States. AMD is broadly divided into two forms, dry andwet, that account for about 85% and 15% of cases, respectively. An earlysign of AMD is the appearance of drusen, which are extracellulardeposits that accumulate on Bruch's membrane, and are thought to derivefrom the overlying retinal pigment epithelium (RPE). Scientists haveproposed that increased autophagy and the release of intracellularproteins via exosomes by the aged RPE may contribute to the formation ofdrusen. Furthermore, a decline in autophagic efficiency in the RPE isassociated with the later pathological stages of AMD and cellulardysfunction.

Protein Restriction in Osteoporosis

Osteoporosis, osteopenia, and other disorders of bone density and/ormineralization can, in certain cases, be treated, prevented, and/or haveits severity or progression lessened in a person by episodic restrictionof the person's bodily intake of protein according to methods andsystems of the subject technology.

Protein Restriction in Chronic Kidney Disease

Chronic kidney disease can, in certain cases, be treated, prevented,and/or have its severity or progression lessened in a person by episodicrestriction of the person's bodily intake of protein according tomethods and systems of the subject technology.

Protein Restriction and Male Pattern Baldness

Male pattern baldness, or alopecia androgenica, is marked typically byhigher levels of 5-alpha-reductase, lower levels of total testosterone,higher levels of unbound/free testosterone, and higher levels of totalfree androgens including DHT. 5-alpha-reductase is responsible forconverting free testosterone into DHT. The enzymes are presentpredominantly in the scalp and prostate. Levels of 5-alpha-reductase areone factor in determining levels of DHT in the scalp. Drugs whichinterfere with 5-alpha-reductase (such as finasteride, which inhibitsthe predominant type 2 isoform) have been approved by the FDA astreatments for hair loss.

Sex hormone-binding globulin (SHBG), which is responsible for bindingtestosterone and preventing its bioavailability and conversion to DHT,is typically lower in individuals with high DHT. SHBG is downregulatedby insulin.

Increased levels of Insulin Growth Factor-1 (IGF-1) have been correlatedto vertex balding, and IGF-1 may be lowered by protein restriction. Highinsulin levels seem a possible link between metabolic syndrome andbaldness. Low levels of SHBG in men and non-pregnant women are alsocorrelated with glucose intolerance and diabetes risk, though thiscorrelation disappears during pregnancy.

By increasing autophagy by protein restriction, destruction of hairfollicles and consequent hair loss can in some cases be delayed orpossibly avoided.

The foregoing description is provided to enable a person skilled in theart to practice the various configurations described herein. While thesubject technology has been particularly described with reference to thevarious figures and configurations, it should be understood that theseare for illustration purposes only and should not be taken as limitingthe scope of the subject technology.

There may be many other ways to implement the subject technology.Various functions and elements described herein may be partitioneddifferently from those shown without departing from the scope of thesubject technology. Various modifications to these configurations willbe readily apparent to those skilled in the art, and generic principlesdefined herein may be applied to other configurations. Thus, manychanges and modifications may be made to the subject technology, by onehaving ordinary skill in the art, without departing from the scope ofthe subject technology.

As used herein, “a period of at least” a particular time (e.g., “aperiod of at least one day”) refers to time period having of a durationof at least as long as that time (e.g., a period lasting one day or morein duration).

As used herein, a phrase such as “instructing that the material beadministered to X” (e.g., a person) can refer either toself-administration by X, or to administration to X by another person oragent, such as a health care worker or a machine, such as a robot.

As used herein, the terms “all protein” and “all of any protein” have atleast their ordinary meaning and are further defined to include allproteins, peptides, polypeptides, and amino acids, free or otherwise, ina particular material, food, meal, other circumstance, or time period ofconsumption, ingestion, or administration.

As used herein, “meal” is a broad term that encompasses its ordinarymeaning and can refer to a food and/or drink (or beverage) portion ofany size, such as a snack or food “treat,” whether frozen, chilled, hot,cookable, microwaveable, reheatable, or raw. Such a meal may be ingestedenterally, such as orally or by gastrostomy.

Any of the methods or systems of periodic or episodic proteinrestriction described herein may be used, as will be evident to oneskilled in the art, for any of the diseases and conditions listed inthis description of the subject technology. The amounts and timing ofmacronutrient administration may be altered or titrated according topatient response.

It is understood that the specific order or hierarchy of steps in theprocesses disclosed is an illustration of exemplary approaches. Basedupon design preferences, it is understood that the specific order orhierarchy of steps in the processes may be rearranged. Some of the stepsmay be performed simultaneously. The accompanying method claims presentelements of the various steps in a sample order, and are not meant to belimited to the specific order or hierarchy presented.

As used herein, the phrase “at least one of” preceding a series ofitems, with the term “and” or “or” to separate any of the items,modifies the list as a whole, rather than each member of the list (i.e.,each item). The phrase “at least one of” can include, but does notrequire, selection of at least one of each item in the series. Rather,the phrase allows a meaning that includes at least one of any one of theitems, and/or at least one of any combination of the items, and/or atleast one of each of the items. By way of example, the phrase “at leastone of A, B, and C” includes at least one of only A, of only B, of onlyC, of any combination of A, B, and C; and/or of each of A, B, and C.

Terms such as “top,” “bottom,” “front,” “rear” and the like as used inthis disclosure should be understood as referring to an arbitrary frameof reference, rather than to the ordinary gravitational frame ofreference. Thus, a top surface, a bottom surface, a front surface, and arear surface may extend upwardly, downwardly, diagonally, orhorizontally in a gravitational frame of reference.

Furthermore, to the extent that the term “include,” “have,” or the likeis used in the description or the claims, such term is intended to beinclusive in a manner similar to the term “comprise” as “comprise” isinterpreted when employed as a transitional word in a claim.

The word “exemplary” is used herein to mean “serving as an example,instance, or illustration.” Any embodiment described herein as“exemplary” is not necessarily to be construed as preferred oradvantageous over other embodiments.

A reference to an element in the singular is not intended to mean “oneand only one” unless specifically stated, but rather “one or more.”Pronouns in the masculine (e.g., his) include the feminine and neutergender (e.g., her and its) and vice versa. The term “some” refers to oneor more. Underlined and/or italicized headings and subheadings are usedfor convenience only, do not limit the subject technology, and are notreferred to in connection with the interpretation of the description ofthe subject technology. All structural and functional equivalents to theelements of the various configurations described throughout thisdisclosure that are known or later come to be known to those of ordinaryskill in the art are expressly incorporated herein by reference andintended to be encompassed by the subject technology. Moreover, nothingdisclosed herein is intended to be dedicated to the public regardless ofwhether such disclosure is explicitly recited in the above description.

While certain aspects and embodiments of the invention have beendescribed, these have been presented by way of example only, and are notintended to limit the scope of the invention. Indeed, the novel methodsand systems described herein may be embodied in a variety of other formswithout departing from the spirit thereof. The accompanying claims andtheir equivalents are intended to cover such forms or modifications aswould fall within the scope and spirit of the invention.

What is claimed is:
 1. A method for providing nutrients to a subject whoat least one of diabetes, hyperinsulinemia, or glucose intolerance,comprising: during a first low-protein time period of at least 4consecutive days, administering nutrient material to the subject suchthat the subject has a bodily intake of protein of less than 20 gramsper day and a bodily intake of carbohydrate of at least 40 percent ofthe subject's bodily intake of energy; wherein the nutrient material isadministrable to at least one of the subject's gastrointestinal tract orintravascular space and comprises carbohydrate; during a firstnormal-protein time period of at least 4 consecutive days that is afterthe low-protein period, administering to the subject a normal dailybodily intake of protein of at least 40 grams; during a secondlow-protein time period of at least 4 consecutive days that is afterfirst normal-protein time period, administering to the subject a bodilyintake of protein of less than 20 grams per day and a bodily intake ofcarbohydrate of at least 40 percent of the subject's bodily intake ofenergy; and during a second second low-protein time period,administering to the subject a normal daily bodily intake of protein ofat least 40 grams.
 2. The method of claim 1, wherein the subject is notcalorie restricted.
 3. The method of claim 1, wherein the subject hastype 2 diabetes.
 4. The method of claim 1, wherein the subject has type1 diabetes.
 5. The method of claim 1, wherein the subject has a bodilyintake of protein of about zero grams per day during the low-proteintime period.
 6. The method of claim 1, wherein the first low-proteintime period is at least 5 consecutive days.
 7. The method of claim 1,wherein the first low-protein time period is at least 6 consecutivedays.
 8. The method of claim 1, wherein the first low-protein timeperiod is at least 7 consecutive days.
 9. The method of claim 1, whereinthe subject's bodily intake of carbohydrate constitutes at least 60percent of the subject's bodily intake of calories during the firstlow-protein time period.
 10. The method of claim 1, wherein thesubject's bodily intake of carbohydrate constitutes at least 80 percentof the person's bodily intake of calories during the first low-proteintime period.
 11. The method of claim 1, wherein the subject's bodilyintake of carbohydrate is at least 100 grams per day during the firstlow-protein time period.
 12. The method of claim 1, wherein carbohydratein the nutrient material constitutes at least 50 percent of the caloriccontent of the nutrient material.
 13. The method of claim 1, whereincarbohydrate in the nutrient material constitutes at least 80 percent ofthe caloric content of the nutrient material.
 14. The method of claim 1,wherein the administering the nutrient material comprises providingindividually packaged servings of the nutrient material.
 15. The methodof claim 1, wherein, during the first normal-protein time period, thesubject receives a bodily intake of all protein of at least 100 grams.16. The method of claim 1, wherein, during the first normal-protein timeperiod, the subject receives a bodily intake of all protein of at least0.6 g per kilogram of the person's body weight.
 17. The method of claim1, wherein, during the first normal-protein time period, the subjectreceives a bodily intake of all protein of at least 0.8 g per kilogramof the subject's body weight.
 18. The method of claim 1, wherein thefirst normal-protein time period is no more than 14 consecutive days.19. The method of claim 1, wherein the subject is not calorierestricted, and the first normal-protein time period is no more than 14consecutive days.